This study proposes to delineate the regulation of extracellular lysosomal hydrolase levels in rat pulmonary tissue. The extracellular concentration of lysosomal hydrolases has been shown to be dependent upon the presence of specific recognition sites on the enzymes which mediates their endocytosis by cells. The study will proceed as follows. 1. To isolate and purify lysosomal hydrolases from rat pulmonary tissue and to characterize their clearance from the circulation by the liver in the intact rat in order to evaluate tissue specificity of enzyme recognition sites for endocytosis of lysosomal enzymes. 2. To demonstrate and characterize the specific endocytosis of lysosomal hydrolases by rat pulmonary tissue using isolated alveolar macrophages and perfused lung preparations. 3. To elucidate the role of serum protease inhibitors in the regulation of extracellular lysosomal protease levels by demonstrating and characterizing the endocytosis of macrophages and perfused lung preparations. An additional objective will be to clarify the possible role of the lysosomal hydrolase recognition sites in endocytosis, transport and distribution of lysosomal hydrolases and the generality of these sites.